Infections in lung cancer patients undergoing immunotherapy and targeted therapy: An overview on the current scenario.

Patients with a diagnosis of lung cancer are often vulnerable to infection, and the risk is increased by tumor-associated immunosuppression and the effects of the treatments. Historically, links between the risk of infection and cytotoxic chemotherapy due to neutropenia and respiratory syndromes are well established. The advent of tyrosine kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)/programmed cell death- ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have changed the treatment paradigm for lung cancer patients.

Early onset metastatic colorectal cancer in patients receiving panitumumab-based upfront strategy: Overall and sex-specific outcomes in the Valentino trial.

Anti-EGFRs plus doublet chemotherapy is considered the optimal upfront option for RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). Early-onset (EO) mCRC has an increasing incidence and its prognostic/predictive role and management is debatable. We performed a post hoc analysis of Valentino study, that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after FOLFOX/panitumumab induction.

Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study.

Introduction: The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available.

Methods: We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity.

Impact of early tumor shrinkage and depth of response on the outcomes of panitumumab-based maintenance in patients with RAS wild-type metastatic colorectal cancer.

Background: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV.

Health-related quality of life in patients with RAS wild-type metastatic colorectal cancer treated with panitumumab-based first-line treatment strategy: A pre-specified secondary analysis of the Valentino study.

Background: Quality of life (QoL) patient-reported outcomes (PROs) data from pivotal first-line trials in metastatic colorectal cancer (mCRC) are poor. The Valentino study showed that de-escalation to single-agent panitumumab after 4-month induction with panitumumab-FOLFOX is inferior to panitumumab-5-FU/LV in patients with RAS wild-type mCRC, although slightly reducing toxicity. We report QoL, a secondary end-point.

The Pan-Immune-Inflammation Value is a new prognostic biomarker in metastatic colorectal cancer: results from a pooled-analysis of the Valentino and TRIBE first-line trials.

Background: Immune-inflammatory biomarkers (IIBs) showed a prognostic relevance in patients with metastatic CRC (mCRC). We aimed at evaluating the prognostic power of a new comprehensive biomarker, the Pan-Immune-Inflammation Value (PIV), in patients with mCRC receiving first-line therapy.

Methods: In the present pooled-analysis, we included patients enrolled in the Valentino and TRIBE trials.

Maintenance Therapy With Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients With RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Few studies are available on the role of maintenance strategies after induction treatment regimens based on anti-epidermal growth factor receptors, and the optimal regimen for an anti-epidermal growth factor receptors-based maintenance treatment in patients with RAS wild-type metastatic colorectal cancer is still to be defined.

Objective: To determine whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment regimen.

Design, Setting, And Participants: This open-label, randomized phase 2 noninferiority trial was conducted from July 7, 2015, through October 27, 2017, at multiple Italian centers.

The Circadian Rhythm of Breakthrough Pain Episodes in Terminally-ill Cancer Patients.

Opioid therapy must be adjusted to the rhythm of a cancer patient's pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients.

Thymidine phosphorylase: the unforeseen driver in colorectal cancer treatment?

5-Fluorouracil- and leucovorin-based chemotherapy regimens are the backbone of colorectal cancer treatment. The addition of oxaliplatin, irinotecan and monoclonal antibodies to this backbone has largely improved clinical outcomes, but has also led to new questions, with conflicting data frequently reported in studies. Thymidine phosphorylase (TP) is a nucleoside-metabolizing enzyme involved in 5-fluorouracil pharmacokinetics, as well as inflammatory responses, neoangiogenesis and apoptosis.

FOLFOX activity in a rare case of metastatic colonic adenocarcinoma of the tongue: a case report.

Background: Adenocarcinomas of the oral cavity are rare neoplasms, and only four cases of primary colonic adenocarcinoma of the tongue have ever been described in literature. Very few information about chemotherapy sensitiveness of this type of neoplasia is available, with only one regimen that showed some activity in a metastatic patient.

Case Presentation: We describe the case of a patient bearing a metastatic colonic adenocarcinoma of the tongue submitted to a first-line chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid (FOLFOX regimen).

A systematic review of the safety profile of the different combinations of fluoropyrimidines and oxaliplatin in the treatment of colorectal cancer patients.

The available fluoropyrimidines and oxaliplatin combinations for colorectal cancer patients have different safety profiles. The aim of this systematic review was to compare their toxicities. The eligible studies were classified as: no bolus; 5-FU single bolus; 5-FU double bolus; capecitabine.

MMC/UFT/LV in refractory colorectal cancer: phase II study and analysis of predictive variables of progression.

Background: The treatment of refractory metastatic colorectal cancer (rmCRC) and the lack of predictive variables are matters of debate.

Patients And Methods: We conducted a multicentre phase II trial assessing the disease control rate (DCR) of the combination of tegafur/uracil and mitomycin C in rmCRC. The number of previous lines of chemotherapy, carcinoembryonic antigen (CEA) levels, progression-free survival of the last chemotherapy regimen (PPFS), and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio at the time of study entry were evaluated as indicators of early progression.

Circannual variation of mitotane and its metabolites plasma levels in patients with adrenocortical carcinoma.

Objectives: Mitotane is the reference drug for the adrenocortical carcinoma treatment; its pharmacological activity seems to depend on drug transformation in two active metabolites: o,p'-DDE (dichlorodiphenylethene) and o,p'-DDA (dichlorodiphenylacetate). Mitotane and metabolites are lipophilic agents; thus, they tend to accumulate into adipose tissues (white and brown), which change their prevalence seasonally. Aim of the work was to evaluate mitotane and metabolites plasma levels variation over the year, in adrenocortical cancer patients treated with Lysodren for at least 6 months.

Treatment of Patients With Metastatic Colorectal Cancer in a Real-World Scenario: Probability of Receiving Second and Further Lines of Therapy and Description of Clinical Benefit.

Background: The optimal therapeutic strategy for metastatic colorectal cancer patients is still a matter of debate. There are no prognostic variables indicating how many lines individual patients ought to receive, and whether later lines could be effective even when earlier ones were not.

Patients And Methods: We retrospectively collected data from 420 consecutive patients with metastatic colorectal cancer at our institution, describing the proportion of patients who received second or later lines of therapy and the chance of a line of treatment being active when the previous line was not.

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis.

Purpose: The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).

Materials And Methods: A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R).

Changes in hepatic perfusion assessed by dynamic contrast enhanced MRI, associated with morphologic evaluation, in patients with liver metastases from colorectal cancer treated with first-line chemotherapy.

Introduction: Blood perfusion of liver metastases can be non-invasively assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The aim of this study was to explore whether the ratio of hepatic arterial to total liver blood flow (Hepatic Perfusion Index-HPI) and the area under the enhancement curve (AUC) of selected liver areas in patients with hepatic metastases from colorectal cancer treated with first-line chemotherapy could predict response and/or be a prognostic variable.

Patients And Methods: Sequential liver DCE-MRI studies with morphological imaging reconstruction were performed in 43 consecutive patients at baseline and every 3 months during oxaliplatin-based first-line chemotherapy.

Systemic treatment of hepatocellular carcinoma: why so many failures in the development of new drugs?

Introduction: The increasing knowledge of the genomic landscape of hepatocellular carcinoma (HCC) and the development of molecular targeted therapies are a promising background for increasing the number of effective drugs for HCC patients. In recent years, many new drugs have been tested as an alternative to sorafenib or after sorafenib failure.

Areas Covered: In this review, our aim is to describe the randomized trials recently conducted in HCC patients, in order to understand the main reasons potentially related to the failures of many drugs.

Unusual paraneoplastic neurological syndrome secondary to a well differentiated pancreatic neuroendocrine tumor: a case report and review of the literature.

Background: Paraneoplastic neurological syndrome (PNS) is a heterogeneous group of disorders affecting any part of the nervous system, in a patient affected by cancer. PNS is estimated to occur in 0.01 to 8% of cancer patients, with higher incidence in those with small cell lung cancer, gynecological tumours or hematological disease.

Acute and fatal thrombocytopenic thrombotic purpura after a single dose of pemetrexed.

Case: Thrombocytopenic thrombotic purpura (TTP), a life-threatening event consisting of disseminated vascular thrombosis, has never been described before as a possible side effect of the anticancer drug pemetrexed. A 70 years old patient affected by a poorly differentiated non small cell lung cancer, subjected to his first pemetrexed administration, developed an acute thrombocytopenic thrombotic purpura, fatal in a few hours.

Conclusions: Pemetrexed can cause TTP.

Intermittent everolimus administration for malignant insulinoma.

Unlabelled: Insulinoma is a rare form of insulin-secreting pancreatic islet cell neuroendocrine (NE) tumor. The medical treatment of the malignant NE disease of the pancreas deeply changed in the last years, thanks to the introduction of new target molecules, as everolimus. Even if the exact mechanism is not actually known, one of the side effects of everolimus, hyperglycemia, has been demonstrated to be useful to contrast the typical hypoglycemia of the insulinoma.

A case of long-term survival after repeated response to oxaliplatin-based chemotherapy and repeated thermoablation of liver metastases from colorectal cancer. Should we introduce the concept of oxaliplatin-resistant tumors?

Background: The management of advanced colorectal cancer patients differs among cancer centers. International guidelines recommend offering all the recognized active regimens in order to obtain survival advantage, but little information is given about the sequence and combination in which such regimens should be administered.

Case Report: We report the case of a man with multiple liver metastasis from colorectal cancer followed for more than 78 months at our Institution.

Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases. The MetaPan study.

Background: Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer.

Methods: Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled.

Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer.

Background: Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy.

Methods: Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data.